Montelukast inhibits inflammatory responses in small airways of the Guinea-pig

Abstract Increased resistance in the small airways is a major contributor of airway obstruction in asthma. The role of leukotrienes (LT) in determining inflammation and obstruction of small size bronchi is not completely understood. Here, we have examined the effect of the cysteinyl-leukotriene ( Cys LT 1 ) receptor antagonist, montelukast, against the bronchoconstriction and inflammatory responses induced by exogenous leukotriene and by allergen challenge in small size (⩽1 mm) Guinea-pig bronchi. Montelukast potently (pA 2 8.3) inhibited the contraction induced by LTD 4 in small bronchi taken from naive Guinea-pigs. Furthermore, montelukast reduced the contraction produced by in vitro ovalbumin (OVA) challenge in small size bronchi from sensitized Guinea-pigs. Montelukast (10 μg kg −1 ) also blocked plasma protein extravasation and accumulation of inflammatory cells (eosinophils) induced by OVA challenge in small intra-parenchymal bronchi of OVA sensitized animals. These findings provide additional evidence that Cys LT 1 receptor antagonism reduces allergic reactions that cause contractile and inflammatory responses in Guinea-pig small airways during OVA challenge. If the anti-bronchospastic and anti-inflammatory actions of the Cys LT 1 receptor antagonists observed in the small airways of Guinea-pigs occur also in man these effects may contribute to the beneficial effects of montelukast in asthmatic patients.